Περίληψη:
Cancer development is an evolutionary process that has been highly
conserved among centuries within organisms. Based on this, the interest
in cancer research focuses on cells, organelles and genes that possess a
genetic conservatism from yeasts to human. Towards this thought,
mitochondria, the highly conserved and responsible for the cellular
bioenergetic activity organelles, might play crucial role in
carcinogenesis. Interestingly, tumors with low bioenergetic signature
have worse prognosis and show a decreased expression of ATPase protein.
Furthermore, according to the stem-cell theory of carcinogenesis,
aggressive tumors are characterized by an increase number of malignant
stem-like cell population and their resistance to chemotherapy has been
found to be mitochondrially driven.
The above considerations triggered us to hypothesize that mitochondrial
bioenergetic processes in stem-like cancer cells plays a crucial role in
the highly conserved process of carcinogenesis. Specifically, we support
that mitochondrial and/or nuclear DNA alterations that control stem
cells’ ATP production drive stem cells to “immortalization” (Otto
Warburg theory) that mediates cancer initiation and progression.
Substantiation of our hypothesis requires evidence that: (1) alterations
in mitochondria bioenergetic metabolites and enzymes encoded either from
the mtDNA or the nuclear DNA are linked to human cancer and (2)
mitochondrial functions are regulated by highly conserved genes involved
in cancer-related cellular processes such as apoptosis, aging and
autophagy. Experimental approach on how this hypothesis might be tested
and promising strategies in cancer therapeutics are also discussed. In
case the hypothesis of stem-cell bioenergetic malformations’ related
carcinogenesis proves to be correct, it would contribute to the
development of new prognostic, diagnostic and even more effective
therapeutic interventions against various types of cancer. (C) 2012
Elsevier Ltd. All rights reserved.
Συγγραφείς:
Hatzi, Vasiliki I.
Terzoudi, Georgia I.
Pantelias, Gabriel E.
and Makropoulos, Vasilios
